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Lecture 17 - Chemical Methods - Disrupt Phospholipoprotein Membrane
Some surfactants act by mimicking phospholipids. Surfactants insert themselves into the cell membrane, distorting and dissolving it, eventually lysing the cell. These are cidal agents and are also toxic to humans if used systematically because it acts on the cell membrane, which is common to both humans and bacteria. Cationic Detergents Cationic detergents have a positive charge, and have the highest activity of all detergents. Cationic detergents are more effective against Gram-positive bacteria because Gram-negative bacteria have an outer membrane that captures the cationic detergent. The outer membrane is still damaged, but it is not as vital as the cell membrane. Cationic detergents do are not very effective against Mycobacterium tuberculosis, hepatitis B, and spores. Hospitals and food industries use these compounds because of their low toxicity and their effectiveness against Staphylococcus and Streptococcus. 'Quaternary Ammonium Compounds' Molecularly, a quaternary ammonium compound is a nitrogen with 4 alkyl groups attached, amongst which there is one long chain of carbons. These compounds are currently used in lysol. 'Benzalkonium Chloride' 'Cetylpyridinium Chloride' 595px-Cetylpyridiniumchlorid.svg.png|Cetylpyridynium Chloride Benzalkonium chloride Structure V.1.svg.png|Benzalkonium Chloride Anionic Detergents Anionic Detergents are not as effective as cationic detergents. They are only effective against weak organisms like Neisseria gonorrhea, Neisseria meningitides, Strep'''tococcus pneumoniae, and Treponema '''pallidum. Sodium Lauryl Sulfate is used as a preservative in some mouthwashes. Bile Salts help emulsify lipids in intestines. They are used in MacConkey's Agar to select for Gram-negative bacteria such as E. coli. They are also used in Taxo P disks to help identify Streptococcus pneumoniae. Non-Ionic Detergents Bland soaps use these as an emulsifier to help clean. They do not have any antimicrobial action, and are more mechanical than chemical. Polymyxins Polymyxins are amino acids that have a polar head and a non-polar tail, similar to the ionic detergents.' Bacillus '''bacteria secrete certain polymixins. Many polymyxins exist (A,B,C,...) but only Polymyxin B and E are used clinically. Polymyxins are not usually drugs of choice because they are '''neurotoxic' and nephrotoxic (toxic to kidneys). They are narrow-spectrum, and are especially effective against Gram-negative bacteria. Polymyxin B Polymyxyn B is a narrow-spectrum drug that is used systemically as a last choice for very resistant Gram-negative organisms such as Acinetobacter and Pseudonomas. It can be used externally for ear infections (otis externa), ophthalmic infections, and as part of the triple-antibiotic ointment alongside of bacitracin and neomycin. Polymyxin E (Colistin) Polymyxyn E is very toxic and usually used externally as a last resort. Also known as colistin, this drug is used in the Thayer Martin Selective Agar. Polyene Antibiotics Polyene antibiotics are cital '''chemicals that bind to sterols in the cell membrane. These affect fungi, which have ergosterol, and humans, which have cholesterol. '''Nystatin Nystatin is not a drug of choice or an alternate, but is still prescribed by doctors. It is used for dermatophytes, superficial fungal infections caused by Candida albicans. Such infections include vulvovaginal candidiasis and oropharyngeal candidiasis. Nystatin is not absorbed by the stomach, so if it is taken orally will not be transferred into the blood stream. It is also used in special mouthwash to clear out Candida Amphotericin B Amphotericin B is the drug of choice for systemic mycoces because it is cital. However, it is also toxic to humans. Amphotericin B treats Zygomycosis, Aspergillosis, and dimorphic fungi. Zygomycosis can be caused by rhizopus, which only grow in dead people and AIDS patients. Dimorphic fungi grow as a yeast at body temperature and as a mold at room temperature, and are also very pathogenic. Azoles Imidazoles have two nitrogen molecules in a ring, which makes it non-soluble in water. This includes Clotrimazole and Miconazole, which are both used for dermatophyte infections, including yeast infections and ringworm. Organisms that cause ringworm include microsporum, trichophyton, and epidermophyton. Ketoconazole is used topically and as an alternate systemically because of its toxicity and inability to cross the blood-brain barrier. Systemically, it treats for systemic mycoses, which is caused by zygomycosis, aspergillosis, and dimorphic fungi. Triazoles include Fluconazole (Diflucan), which is the drug of choice for superficial and deep yeast infections, and Voriconazole, which is the drug of choice for systemic mycoses because it can penetrate the blood-brain barrier.